Abstract
BackgroundAlcohol consumption is associated with haemostasis and so may influence cardiovascular conditions. It is unknown whether the association of alcohol with total and γ’ fibrinogen concentrations, as well as clot structure, are modulated by fibrinogen and factor (F) XIII single nucleotide polymorphisms (SNPs).MethodsTotal fibrinogen, γ’ fibrinogen and clot properties of 2010 healthy Africans residing in South Africa were measured in relation to alcohol intake as well as its markers – gamma-glutamyltransferase (GGT), percentage carbohydrate deficient transferrin (%CDT), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). Fourteen fibrinogen and two SNPs in the FXIII gene were genotyped to determine their influence.ResultsAlcohol intake and its markers correlated negatively with fibrinogen and clot lysis time (CLT) as well as with most of the clot properties. Percentage γ’ fibrinogen correlated positively with AST and negatively with alcohol intake. We then stratified for alcohol intake and found inverse associations between γ’ fibrinogen and both %CDT and GGT–CDT in consumers, but the positive association with AST remained only in abstainers. Alcohol intake and its markers modulated the influence of fibrinogen SNPs on total fibrinogen concentrations and the fibrinogen SNPs as well as an FXIII SNP on clot density (all p < 0.004).Conclusion/sWe show for the first time that some individuals harbour certain genotypes that, in combination with alcohol consumption, might predispose or protect them from haemostatic factors that might lead to the development of cardiovascular disease. Studies are needed to clarify the mechanisms related to the interplay between alcohol and the gene variants observed here.
Highlights
Alcohol consumption is associated with haemostasis and so may influence cardiovascular conditions
The circulating glycoprotein fibrinogen [6, 7], and its splice variant γ’ fibrinogen [8], that provide the main structure for blood clots; as well as factor XIII (FXIII) that stabilises the formation of clots and clot structure [9] have been implicated in cardiovascular disease (CVD) [10]
To clarify the interrelationships of these factors, we conducted a study with the aim to establish, first, what associations there might be between total and γ’ fibrinogen concentration or fibrin plasma clot properties and alcohol intake/markers; and second, to determine whether there are interactions between these alcohol biomarkers and fourteen fibrinogen and two FXIII gene single nucleotide polymorphisms (SNPs), that we identified from the literature to be of importance, in relation to total and γ’ fibrinogen concentrations and clot characteristics
Summary
Alcohol consumption is associated with haemostasis and so may influence cardiovascular conditions. It is unknown whether the association of alcohol with total and γ’ fibrinogen concentrations, as well as clot structure, are modulated by fibrinogen and factor (F) XIII single nucleotide polymorphisms (SNPs). Alcohol intake is one such factor that influence CVD risk – consumed in light to moderate amounts risk decreases [3], whereas binge drinking increases it [4]. Moderate alcohol consumption reduces total fibrinogen concentrations [11,12,13,14]. Whether alcohol intake influences γ’ fibrinogen is unknown. The impact of alcohol on the properties of blood clots is complex and remains to be elucidated [15]
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